Venezuelan equine encephalitis virus (VEEV) is a neurotropic alphavirus transmitted by mosquitoes that causes encephalitis and death in humans1. VEEV is a biodefence concern because of its potential for aerosol spread and the current lack of sufficient countermeasures. The host factors that are required for VEEV entry and infection remain poorly characterized. Here, using a genome-wide CRISPR-Cas9-based screen, we identify low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3)-a highly conserved yet poorly characterized member of the scavenger receptor superfamily-as a receptor for VEEV. Gene editing of mouse Ldlrad3 or human LDLRAD3 results in markedly reduced viral infection of neuronal cells, which is restored upon complementation with LDLRAD3. LDLRAD3 binds directly to VEEV particles and enhances virus attachment and internalization into host cells. Genetic studies indicate that domain 1 of LDLRAD3 (LDLRAD3(D1)) is necessary and sufficient to support infection by VEEV, and both anti-LDLRAD3 antibodies and an LDLRAD3(D1)-Fc fusion protein block VEEV infection in cell culture. The pathogenesis of VEEV infection is abrogated in mice with deletions in Ldlrad3, and administration of LDLRAD3(D1)-Fc abolishes disease caused by several subtypes of VEEV, including highly virulent strains. The development of a decoy-receptor fusion protein suggests a strategy for the prevention of severe VEEV infection and associated disease in humans.Endogenous viral elements (EVEs)-viruses that have integrated their genomes into those of their hosts-are prevalent in eukaryotes and have an important role in genome evolution1,2. The vast majority of EVEs that have been identified to date are small genomic regions comprising a few genes2, but recent evidence suggests that some large double-stranded DNA viruses may also endogenize into the genome of the host1. Nucleocytoplasmic large DNA viruses (NCLDVs) have recently become of great interest owing to their large genomes and complex evolutionary origins3-6, but it is not yet known whether they are a prominent component of eukaryotic EVEs. Here we report the widespread endogenization of NCLDVs in diverse green algae; these giant EVEs reached sizes greater than 1 million base pairs and contained as many as around 10% of the total open reading frames in some genomes, substantially increasing the scale of known viral genes in eukaryotic genomes. These endogenized elements often shared genes with host genomic loci and contained numerous spliceosomal introns and large duplications, suggesting tight assimilation into host genomes. https://www.selleckchem.com/products/isoproterenol-sulfate-dihydrate.html NCLDVs contain large and mosaic genomes with genes derived from multiple sources, and their endogenization represents an underappreciated conduit of new genetic material into eukaryotic lineages that can substantially impact genome composition.Near a magic twist angle, bilayer graphene transforms from a weakly correlated Fermi liquid to a strongly correlated two-dimensional electron system with properties that are extraordinarily sensitive to carrier density and to controllable environmental factors such as the proximity of nearby gates and twist-angle variation. Among other phenomena, magic-angle twisted bilayer graphene hosts superconductivity, interaction-induced insulating states, magnetism, electronic nematicity, linear-in-temperature low-temperature resistivity and quantized anomalous Hall states. We highlight some key research results in this field, point to important questions that remain open and comment on the place of magic-angle twisted bilayer graphene in the strongly correlated quantum matter world.Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.The journey of RNA polymerase II (Pol II) as it transcribes a gene is anything but a smooth ride. Transcript elongation is discontinuous and can be perturbed by intrinsic regulatory barriers, such as promoter-proximal pausing, nucleosomes, RNA secondary structures and the underlying DNA sequence. More substantial blocking of Pol II translocation can be caused by other physiological circumstances and extrinsic obstacles, including other transcribing polymerases, the replication machinery and several types of DNA damage, such as bulky lesions and DNA double-strand breaks. Although numerous different obstacles cause Pol II stalling or arrest, the cell somehow distinguishes between them and invokes different mechanisms to resolve each roadblock. Resolution of Pol II blocking can be as straightforward as temporary backtracking and transcription elongation factor S-II (TFIIS)-dependent RNA cleavage, or as drastic as premature transcription termination or degradation of polyubiquitylated Pol II and its associated nascent RNA. In this Review, we discuss the current knowledge of how these different Pol II stalling contexts are distinguished by the cell, how they overlap with each other, how they are resolved and how, when unresolved, they can cause genome instability.Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.